PB1840: OUTCOME OF ADULT ACUTE MYELOID LEUKEMIA PATIENTS WITH EXTRAMEDULLARY DISEASE AFTER TREATMENT WITH VENETOCLAX/HYPOMETHYLATING AGENTS
Authors: Sabine Kayser, Khaled Sanber, Giovanni Marconi, Agnese Mattei, Marlise Luskin, Amar Kelkar, Marco Cerrano, Chiara Sartor, Fabio Giglio, Marta Riva, Lorenzo Rizzo, Francesco Saraceni, Selene Guerzoni, Federica Lessi, Erika Borlenghi, Alexander Perl, Mark J Levis, Cristina Papayannidis, Tania Jain, Richard Schlenk
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Extramedullary (EM) manifestations of acute myeloid leukemia (AML) are rare, but have a broad clinical spectrum. EM has traditionally been approached with conventional chemotherapy (CTX) and/or radiation. Recently, venetoclax (VEN) in combination with hypomethylating agents (HMA) or low-dose cytarabine was approved for treatment of newly diagnosed AML patients (pts) who are ≥ 75 years or who are ineligible for intensive CTX due to comorbidity. Whether EM AML responds to VEN/HMA is not known. Aims: To characterize adult pts with EM AML and evaluate outcome after VEN/HMA treatment within an international retrospective cohort analysis. Methods: We studied 41 pts (median age, 66 years; range, 19-81 years) treated with VEN/HMA between 2017 and 2022. Eighteen (44%) of 41 pts were relapsed or refractory after intensive CTX or allogeneic hematopoietic stem cell transplantation (allo-HCT; n=10/18) prior to VEN/HMA. Up to 31 VEN/HMA cycles (median, 2 cycles; ≤2 cycles, n=23; 3-4 cycles, n=10; ≥5 cycles, n=8) were administered according to the previously approved regimens. EM response assessment was performed by CT or PET-CT and bone marrow (BM) and/or cerebral fluid/MRI evaluation in case of central nervous system involvement. Results: Type of AML was de novo in 23 (56%), secondary after myelodysplastic syndrome/myeloproliferative neoplasm in 17 (41%), and therapy-related in 1 (3%) patient. Median white blood cell and platelet counts at time of EM presentation were 6.6/nl (range, 0.6-131.2/nl) and 66/nl (range, 6-307/nl), respectively. Fifteen pts (37%) were female; ECOG was ≤2 in all pts. Overall, pts had in median 2 EM manifestations (range, 1-5; Table 1). In addition to EM disease, n=34 (83%) pts had BM involvement. Cytogenetic analysis was performed in 38 (93%) pts. Seventeen (45%) pts showed a complex karyotype, 9 (24%) a normal karyotype and 12 (31%) pts other abnormalities. NPM1 was mutated in 8 (20%) and 3 (7%) pts had a FLT3-ITD mutation. TP53 and spliceosomal mutations could be detected in 11 (27%), each. Risk classification according to ELN 2022 was low-risk in 5 (12%), intermediate-risk in 13 (32%) and high-risk in 20 (49%) of the pts (missing, n=3; 7%). Eighteen (44%) pts achieved CR/CRi after VEN/HMA treatment, of whom 3 were heavily pretreated including allo-HCT. Five (12%) pts achieved a partial remission (PR) and 4 (10%) stable disease. The overall response rate (ORR; including CR/CRi/PR) was 56% (n=23). Six pts went on to allo-HCT (CR/CRi, n=4; PR, n=2). Prior to allo-HCT all pts received ≤4 cycles (2 cycles, n=3; 1/3/4 cycles, n=1, each). Conditioning was dose-reduced in 4 and myelo-ablative in 2 pts. Median follow-up was 28.8 months (95%-CI, 11.5 months - not reached) and median overall survival (OS) 6.4 months (95%-CI, 3.9-12 months). One-year and 2-years OS rates were 26.4% (95%-CI, 15-47%) and 14% (95%-CI, 5-36%), respectively. Age with a cut-off of 60 years had no impact on OS (P=0.80). Relapse occurred in 11 of 18 (61%) pts who had achieved CR/CRi after VEN/HMA treatment. Of those, all except than two succumbed of their disease. Five (28%) pts are in ongoing CR/CRi and 2 died in CR. All pts who did not respond died due to disease progression. Summary/Conclusion: In our group of pts with high-risk features, treatment with VEN/HMA resulted in an encouraging ORR of 56% with a CR/CRi rate of 44%. However, VEN/HMA alone may not be effective in maintaining disease control. Whether allo-HCT after disease control with VEN/HMA is a veritable option needs to be evaluated in the future.Keywords: Acute myeloid leukemia, Venetoclax, Clinical outcome